Warfarin: Influence of Genetic Variations and Their Prevalence in Indian Population | Chapter 1 | Medicine and Medical Research: New Perspectives Vol. 1

 

Warfarin has been the most trusted but challenging anticoagulant in clinical practice for the last seven decades. The challenge is to manage its dose. A narrow therapeutic index and high inter- and intra-individual variability in drug disposition and response are the factors that shift the pendulum to adverse drug events from one end of fatal hemorrhage to the other i.e. thrombosis. The difficult task for clinical management is to maintain the required international normalized ratio (INR) with warfarin therapy. Factors responsible for this difficult task include both genetic and non-genetic. The predominant genes are those coding for vitamin K epoxide reductase complex (VKORC) subunit 1 (VKORC1; the target of warfarin and the enzyme of warfarin metabolism; cytochrome P450 enzyme 2C9 (CYP2C9). There is general agreement among published retrospective population studies that the combination of VKORC1 and CYP2C9 genotypes, together with gender, age, body mass index or height or weight and concurrent medications, predict approximately 50% of warfarin dose requirement. Thus, genetic testing will be able to predict and help in directing toward the correct dose and reduce the counts of trial and error as well as risks during therapy. Within the Asian population, Indian patients have been reported to require higher warfarin doses than others. Here we also review the prevalence of the genetic variations of VKORC1 and CYP2C9 associated with variable warfarin response in Indian populations from different regions and also depict studies that have aimed at analysing the influence of genotypic variations to the clinical dose of Warfarin in the Indian population.

 

 

Author(s) Details

Kavita Shalia
Sir H. N. Medical Research Society, Sir H. N. Hospital and Research Centre, Court House, L. T. Road, Mumbai 400002, India.

Sunila Raju
Sir H. N. Medical Research Society, Sir H. N. Hospital and Research Centre, Court House, L. T. Road, Mumbai 400002, India.

Amit Chandan
Sir H. N. Reliance Foundation Hospital and Research Centre, Raja Rammohan Roy Road, Mumbai 400004, India.

 

Please see the link:- https://doi.org/10.9734/bpi/mmrnp/v1/1194

Role of Gene Polymorphisms Might Contribute to Endometriosis Susceptibility | Chapter 9 | Current Innovations in Medicine and Medical Science Vol. 5

 Endometriosis is a condition in which the tissue that normally lines the uterus grows outside the uterus. Endometriosis is characterized by the presence of tissue attached to the ovaries, fallopian tubes, or intestines. Several recent studies have examined genetic polymorphisms as possible factors in the development of endometriosis. The purpose of this study is to review case-control studies of recent data on genes with nucleotide polymorphisms associated with endometriosis. A PubMed search of endometriosis, polymorphisms, and interleukins found 50 publications between 2001 and 2020. These were classified according to the type of polymorphism tested and whether the results supported or did not support an association with endometriosis. We have found a whole range of conflicting results. About half of the studies surveyed found an association between various polymorphisms and endometriosis. Based on this review, it can be concluded that there are strong gene-environment interactions that could certainly influence approaches to identify genetic variants associated with endometriosis.

Author(s) Details:

Nandhini Balunathan,
Department of Human Genetics, Faculty of Biomedical sciences and technology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai-116, India.

S. Nandhini,
Department of Human Genetics, Faculty of Biomedical sciences and technology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai-116, India.

J. Akshaya,
Department of Human Genetics, Faculty of Biomedical sciences and technology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai-116, India.

Please see the link here: https://stm.bookpi.org/CIMMS-V5/article/view/8467

Methylenetetrahydrofolate Reductase Gene and Potential Risk to Autism Spectrum Disorder | Chapter 13 | New Horizons in Medicine and Medical Research Vol. 7

 The goal of this study was to see if the methylenetetrahydrofolate reductase (MTHFR) variations in the Saudi community altered susceptibility to the risk of autistic spectrum disorder (ASD).

Methods and Subjects: The severity of ASD symptoms was assessed using diagnostic and statistical manual of mental disorders (DSM-V) criteria and scores on the childhood autism rating scale (CARS). TaqManTM genotyping assays for the 677C>T rs1801133 and 1298A>C rs1801131 SNPs in the MTHFR gene were used to assess genomic DNA from buccal cells of 112 patients with ASD and 104 healthy controls. The optimum interactive inheritance method for selected SNPs was determined using the SNPStats software (https://www.snpstats.net). The protein-protein interaction network of the MTFR gene was predicted using the Search Tool for the Retrieval of Interacting Genes (STRING) database (https://string-db.org).

Controls in the studied SNPs were compatible with Hardy-Weinberg equilibrium. The MTHFR rs1801133 C>T and MTHFR rs1801131 A>C SNPs were shown to have associated with ASD risk (odds ratio [OR]= 5.2 and 22.2, respectively). In cases vs controls, genotype relationships of these SNPs were statistically significant (P= 0.0012 and P= 0.0008, respectively). The SNPs studied were shown to be strongly linked to ASD cases with a score of 37 (codominant and recessive models; P= 0.001 and P= 0.0005, respectively). The C/C-A/A genotype was the most prevalent among six combination genotypes in ASD cases (42.9 percent ). A substantial variation in haplotype distribution between patients and controls was found in a global haplotype analysis (P=0.00057). The two SNPs were discovered to be in linkage disequilibrium (D'= 0.63, r2 = 0.260).

Conclusion: The MTHFR rs1801133 and rs1801131 SNPs interact to increase the risk of ASD, particularly when verified in larger cohorts with other genetic/environmental factors. Our findings could be used to support future genetic association research in the Saudi population, as well as government and health-care professionals working on regional health-management efforts.

Author(S) Details

Nasser A. Elhawary
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Mecca 21955, P.O. Box 57543, Saudi Arabia.

View Book:- https://stm.bookpi.org/NHMMR-V7/article/view/6671

Integrated Risk Assessment Coupled with Molecular Detection Platform Enhance Personalized Health Care in Metabolic Disorders | Chapter 13 | Emerging Trends in Disease and Health Research Vol. 3

 Type 2 diabetes mellitus (T2DM) is characterised by multidimensional metabolic dysfunction caused by endothelium and beta cell malfunction, as well as regulatory molecular dysfunction caused by stress, lifestyle, food, and physical inactivity anchored in the insulin signalling network. It is caused by both environmental and genetic changes, which may play a role in the development of secondary disease as a risk barrier for microvascular disorders such coronary artery disease, hypertension, obesity, stroke, and dyslipidemia. It's also worth noting that T2DM is a risk factor for mental illness accompanied by cognitive impairment, such as Alzheimer's disease (AD). Using integrated multi-omics techniques, new evidence suggests that the interrelationship between metabolic syndrome and mental disorders involves multiple biological interfaces and connectivity. This review summarises that these categories include core omics strategy, genomics, transcriptomic, and proteomics; advanced omics applications, such as nutrigenomics, and metabolomics, to better understand pathobiology in metabolic illness and improve prediction skill set of T2DM with complicated genetic background and heterogeneity traits. Diagnostic indicators such as glucose concentrations and haemoglobin A1c are being employed in the blood to predict the state of metabolic surveillance. The human whole genome sequencing project ushered in the post-genomic era. Diet and lifestyle have exhibited dual qualities to be employed in customised dietary medicine as treatment guidance and precision medicine for health surveillance, both of which are dependent on genetic diversity as illustrated by gene-diet interaction. Molecular-based risk assessment using Omics methods such as nutrigenomics and metabolomics can help forecast and prevent health difficulties caused by environmental risk and exposure in people who have adapted to the new post-industrialized niche.

Author(S) Details

Sylvester Ndimele
Department of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY, 10595, USA.

Miranda L. Carpenter
Department of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY, 10595, USA.

Jae-Hyeon Cho
Institute of Agriculture and Life Science, Collegeof Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Korea.

Diane E. Heck
Department of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY, 10595, USA.

Hong Duck Kim
Department of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY, 10595, USA.

View Book:- https://stm.bookpi.org/ETDHR-V3/article/view/5889

Cardiovascular Disease (CVD) and Genomics Imbalance to Risk Oxidative Stress Following Environmental Stress: Molecular Vitality for Prediction and Prevention | Chapter 01 | Current Aspects in Pharmaceutical Research and Development Vol. 7

 Cardiovascular disease (CVD) is one of the most costly health problems, requiring individualised preventative systems that include a variety of pharmacological alternatives. It manifests itself in a variety of ways as a result of risk factors (such as smoking, a high-fat diet, alcohol, stress, and sedentary behaviour) that can lead to microvascular dysfunction (e.g., artery disorders), myocardial infarction (MI), arrhythmias, angina, and atherosclerosis. There is still some bias in CVD pathogenesis and endpoint variance between plaque development and risk variables originating from intrinsic (or hereditary risk) or extrinsic (or environmental risk) sources (or environmental risk). Lipoprotein has been shown to have a significant impact on blood flow and plaque development in prior research. Furthermore, there is sufficient evidence to link various risk factors in a patient's history, such as high blood pressure, vascular injury to the heart, and metabolic problem, to diets that may contribute to heart failure and stroke in clinic and animal models, such as apoE transgenic animals. In this report, we examine molecular tools (i.e., multidimensional Omics or systemic biology with various detection modules such as genomics, proteomics, metabolomics, and pharmacogenomics, among others) for supporting early prediction and prevention of patient exposure to environmental risks, as well as conducting systematic health care aligned with surveillance and monitoring, including molecular sensitivity and validation combined with traditional imaging systems in therapeutic and prevention options.

We used Genomics to visualise the patient's genetic variation or polymorphism by comparing DNA sequences to individuals who were not impacted. These results are valuable in determining which genes have been altered and who is more vulnerable due to their genetic composition. Furthermore, proteomics will aid in the investigation of target proteins, including their locations, structures, and activities, in order to better manage cardiopathy or cardiac dysfunction. Metabolomics is an Omics technology used to investigate medication efficacy and metabolism in cardiopathies transmission. Furthermore, identifying metabolites can improve one's understanding of metabolic pathways related to high-fat diets, as well as how certain environmental and genetic factors related to blood flow, as well as altered molecular networks in plaque formation, can influence cardiac dysfunction and its regulatory pathways. Finally, pharmacogenomics will aid in the development of effective treatments on a more individualised basis, ensuring that everybody with a metabolic condition or hypertension has a chronic disease propensity pattern. This will highlight the importance of systemic detection using molecular techniques by integrating to target, Lipoproteins, the correct focus in early cardiomyopathy, and validation in various therapy endpoints to assure quality outcomes.

Author(S) Details

Aleq M. Jaffery
Department of Public Health, Division of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY, USA.

Yoon Ju Lee
Department of Public Health, Division of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY, USA.

Diane E. Heck
Department of Public Health, Division of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY, USA.

Hong Duck Kim
Department of Public Health, Division of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY, USA.

View Book:- https://stm.bookpi.org/CAPRD-V7/article/view/5409